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Moffitt Clinical and Translational Phase I Trial Examines Targeted and Sequence-Specific Therapy to Improve Chemotherapy Treatment
volume 6 | issue 7
July 2007Pages: 999 - 1000
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Doctors at H. Lee Moffitt Cancer Center & Research Institute are examining the results of a targeted and sequence-specific therapy meant to improve the effects of chemotherapy in cancer patients via the use of a sensitizing agent prior to chemotherapy treatment.
The clinical and translational Phase I trial describing this therapy in patients with advanced solid tumor malignancies was recently published in the Journal of Clinical Oncology. The study goal was to determine the safety, toxicity and maximum-tolerated dose of a sequence-specific combination of the histone deacetylase inhibitor (HDACi), valproic acid (VPA), and the anthracycline chemotherapeutic agent, epirubicin. The study also sought to define the clinical feasibility of VPA as an HDACi.
"We found VPA to be a particularly effective HDACi and sensitization agent when administered 48 hours prior to epirubicin treatment. This approach works to open up the chromatin structure prior to chemotherapy, enabling accessibility of the chemotherapeutic agent to targets on the DNA", said Dr. Pamela Munster, who conducted the study and is a member of Moffitt's Division of Experimental Therapeutics and Breast Oncology.
The results of the trial found exceptional response rates among the 48 patients who enrolled with acceptable toxicity. Noteworthy anti-tumor activity was not only observed in heavily pretreated patients but also in patients with historically anthracycline-resistant tumors. Objective responses were seen in 22 percent of patients.
The study was supported by grants from the National Institutes of Health and The Susan G. Komen Breast Cancer Foundation. Pfizer Global Research and Development supplied the anthracycline. The study describes the first use of an HDACi to sensitize cancer cells to an anthracycline in patients with solid tumors.
"Our strategy is not to replace chemotherapy but to significantly improve its effectiveness and benefits for patients. We were pleased with the response rate of this study and are hopeful as we move into a limited phase II trial in patients with metastatic breast cancer," said Munster.
About H. Lee Moffitt Cancer Center & Research Institute Located in Tampa, Florida on the University of South Florida campus, H. Lee Moffitt Cancer Center & Research Institute (www.moffitt.org) is the only Florida-based cancer center with the NCI designation as a Comprehensive Cancer Center for its excellence in research and contributions to clinical trials, prevention and cancer control. Moffitt currently has 15 affiliates in Florida, one in Georgia and two in Puerto Rico. Additionally, Moffitt is a member of the National Comprehensive Cancer Network, a prestigious alliance of the country's leading cancer centers, and is listed in U.S. News & World Report as one of America's Best Hospitals for cancer. Moffitt's sole mission is to contribute to the prevention and cure of cancer.
This is an open-access article
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.